Over 250 blood group determinants are known and most of these are located on integral red cell proteins and glycoproteins. The functions of some of these structures are known: Diego (band 3) is the red cell anion exchanger; Kidd, a urea transporter; Colton (aquaporin 1), a water channel; Cromer (DAF) and Knops (CRI), complement regulators; Diego (band 3) and Gerbich (glycophorin C/D) link the red cell membrane and the membrane skeleton. The Duffy glycoprotein is a chemokine receptor that may act as a scavenger for inflammatory mediators in the peripheral blood, but is also exploited as a receptor by Plasmodium vivax merozoites. The functions of some blood group antigens can be speculated upon because of structural similarity to proteins and glycoproteins of known function. For example, the Lutheran, LW, and Ok glycoproteins are members of the immunoglobulin superfamily of receptors and signal transducers, the Rh proteins and related glycoproteins show homology to ammonium transporters, and the Kell glycoprotein resembles a family of endopeptidases. Yet most blood groups systems contain null phenotypes associated with no apparent pathology. If these blood group antigens have important functions, other structures must be able to carry out those functions in their absence. Almost nothing is known of the biological significance of blood group polymorphism.